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Biomedical subjects

K Ishida

Publications and source records attributed to K Ishida.

At least 361 records · Page 20Linked to original sources
PubMed1993

The effects of aging on the function of alveolar macrophages in mice.

In order to determine whether the function of alveolar macrophages (AM) is modulated by aging, we measured the TNF-alpha production, phagocytic function, and surface antigen expression of AM from young and old mice. When AM were primed by IFN-gamma (500 units/ml) and triggered by LPS (100 micrograms/ml), TNF-alpha production by AM was significantly smaller in old mice as compared with young mice (young mice: 161.7 +/- 28.2 units/ml; old mice: 89.3 +/- 13.6 units/ml, P < 0.05). The percentage of AM which phagocytosed latex particles (more than one particle) in old mice was significantly lower than in young mice (young: 78.1 +/- 2.5%; old: 62.8 +/- 3.4%, P < 0.05). Ia antigen expression of the AM was significantly higher and asialo-GM1 antigen expression was significantly lower in old mice than in young mice (Ia: young, 0.030 +/- 0.005; old, 0.092 +/- 0.024, P < 0.05; asialo-GM1: young, 0.-9 +/- 0.01; old, 0.75 +/- 0.07, P < 0.01). These results suggest that alveolar macrophage function is at least decreased in part with aging in mice.

Aging↗
PubMed1993

Studies on hemolytic action of a hemolysin produced by Vibrio mimicus.

Some properties and mechanism of action of a hemolysin (VMH) produced by an enteropathogenic Vibrio mimicus strain was examined. VMH was heat-labile and inhibited by addition of divalent cations, including Ca2+, Mg2+ and Mn2+. The hemolysis by VMH was inhibited by incubating with gangliosides, suggesting that the ganglioside was the binding site on the erythrocyte membrane for VMH. Existence of a galactose moiety on reducing end of the ganglioside molecule and a sialic acid on the galactose moiety was suggested to be important for the binding of VMH molecule. Colloid osmotic manner of the hemolysis by VMH was demonstrated.

Animals↗
PubMed1993

Ablation of eosinophils with anti-IL-5 antibody enhances the survival of intracranial worms of Angiostrongylus cantonensis in the mouse.

Effects of depressed eosinophilia on the development of Angiostrongylus cantonensis in the mouse were studied using monoclonal rat anti-mouse-interleukin-5 antibody (anti-IL-5). The administration of anti-IL-5 strongly depressed peripheral, cerebrospinal fluid (CSF) and medullary eosinophilic responses in mice infected with A. cantonensis, when compared with groups treated with phosphate-buffered saline solution (PBS) alone or isotype-matched rat IgG. There was no significant difference in A. cantonensis antigen specific IgG and IgE antibody responses between rat IgG treated and anti-IL-5 treated mice. Intracranial worm recovery in anti-IL-5 treated mice was consistently high throughout the course of the study and some worms migrated from the brain to the lungs. By contrast, almost all the intracranial worms in the mouse groups treated with PBS alone or rat IgG died before day 32. These data clearly indicate that IL-5 is essential for eosinophil responses in A. cantonensis infected mice and also that eosinophils serve as a potential effector cell in the killing of the intracranial worms in mice.

Angiostrongylus cantonensis↗
PubMed1993

Role of leukotrienes in airway hyperresponsiveness in guinea-pigs.

1. Repeated aerosolization of leukotriene C4 (LTC4) to guinea-pigs produced leftward shift in their pulmonary resistance (RL) dose-response curves to inhaled acetylcholine (ACh) without increasing the maximum responses. 2. Repeated LTC4 aerosolization did not increase airway eosinophils. 3. The 5-lipoxygenase-activating protein (FLAP) inhibitor, MK-886, prevented the leftward shift in RL dose-response curves to ACh following repeated antigen challenge in guinea-pigs. 4. MK-886 did not inhibit the increased maximal RL produced by repeated antigen challenge, nor inhibit the airway eosinophilia induced by repeated antigen challenge. 5. Our findings suggest that leukotrienes may account for the leftward shift in pulmonary resistance responses caused by antigen but do not cause the airway eosinophilia nor enhanced maximum broncho-constrictor response to antigen.

5-Lipoxygenase-Activating Proteins↗
PubMed1993

Circulating autoantibody to mature neurons and astrocytes of humans and some mammals present in a demented patient with autoimmune disorder.

Circulating autoantibody to a 48-kD nuclear protein in neurons and astrocytes of the human and bovine cerebrum were present in the serum of a demented patient with an autoimmune disorder. Other human visceral organs, dorsal root ganglion cells, neuroblastoma and glioblastoma cell lines, and rat cerebrum did not react with the patient's serum. No sera from age-matched controls, including those with Alzheimer's disease, reacted with the 48-kD protein. Only the mature neurons and astrocytes of humans and some mammals express the 48-kD protein. This antibody may be responsible for the patient's demented condition.

Aged↗
PubMed1993

Plasma glucagon responses to insulin-induced hypoglycemia and arginine in spontaneous non-insulin-dependent diabetes mellitus (NIDDM) rats, Otsuka Long Evans Tokushima Fatty (OLETF) strain.

Pancreatic A-cell function in the newly developed Otsuka Long Evans Tokushima Fatty (OLETF) strain of non-insulin-dependent diabetes mellitus (NIDDM) rats was examined in relation to the morphological changes in their islets and the plasma glucagon responses to insulin-induced hypoglycemia and an arginine test by chronological studies in seven male OLETF and seven male non-diabetic control Long Evans Tokushima Otsuka (LETO) rats each at 10, 16 and 24 weeks of age and eight male OLETF rats that were placed in a cage with a wheel for exercising from 5 to 24 weeks of age. The hormonal contents and morphological features of the pancreas of these rats were examined. After iv injection of insulin, the plasma glucagon level rose significantly from the basal level in OLETF rats at 10 weeks old, but little if at all in those of 16 and 24 weeks old. The pancreatic A cells of LETO rats of all age groups responded equally well to glucopenia. The areas under the response curves of plasma glucagon (sigma delta IRG) during the 90 min of insulin-induced hypoglycemia were 14496 +/- 7860 vs 9588 +/- 3930, 2257 +/- 3018 vs 9235 +/- 5447 (p < 0.05) and 826 +/- 985 vs 9707 +/- 2510 (p < 0.01) ng.min-1.l-1 in OLETF rats vs LETO rats of 10, 16 and 24 weeks old, respectively. The plasma glucagon responses during the arginine test were higher in OLETF rats than in LETO rats at 10 and 16 weeks but not at 24 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Radical trapping by PBN during reperfusion in rabbit gastric mucosa.

Oxygen free radicals have been considered as a cause of ischemia-reperfusion injury in several organs, but this injury in a stomach, containing acid, may progress to severe damage. Thus, we examined the effect of ischemia-reperfusion and milk-intake on rabbit gastric mucosa. The gastric mucosal blood flow was increased after milk-intake, and gastric rupture was detected. Superoxide dismutase activity measured by an improved nitroblue tetrazolium reduction method and thiobarbituric acid reactive substances in serum is increased during ischemia-reperfusion and milk-intake. By using alpha-phenyl N-tert-butyl nitrone (PBN) as a spin trap and electron paramagnetic resonance (EPR), we detected lipidic radicals from tissue samples in chloroform-methanol solvent only during reperfusion and milk-intake period; no signal was detected before. The EPR signal of spin adducts obtained in the sample after ischemia-reperfusion and milk-intake would be a mixture of peroxyl and alkoxyl radicals from the analysis of coupling constants.

Animals↗
PubMed1993

[An aspiration pneumonia in acute airway damage model induced by HCl and/or LPS].

The purpose of this study is to evaluate chemical and pathological changes of the lung and to elucidate the role of TNF alpha and elastase in acute lung injury induced by HCl or lipopolysaccharide (LPS). Anesthetized rats were injected with pH 1.4 0.7 ml/kg body weight of HCl and 0.5 mg/kg body weight (BW) of LPS (E. coli) into the lung. Acute tracheal injury model (Mendelson Syndrome) were made. Control animals received only saline. Animals were sacrificed 1, 6, or 12 hours after the HCl or LPS or HCl and LPS injection, bronchoalveolar-lavage (BAL) was performed in the same way in control and experimental groups. The other animals which were treated as well were excised by histology. There was neither increase in TNF alpha-production nor increase in neutrophils resulting from HCl injection only. Elastase-like activity was not detected in animals treated only with HCl. However, 1 hour after LPS injection, the production of TNF alpha (37.0 +/- 8.0 Units/ml) was significantly greater than that of the control group (12.1 +/- 4.2 Units/ml) in BALF. Six hours after HCl and LPS injection, the concentration of elastase-like activity (0.023 +/- 0.002 nM) was significantly greater than that of the LPS group (0.011 +/- 0.001 nM). Only patches of intraalveolar hemorrhage and elevation of fibrin was observed in the HCl injected rats at 1 hour after injection. Six hours after LPS injection, the alveolar spaces were filled with large amounts of neutrophils. These findings suggest that TNF alpha and elastase play a significant role in HCl and LPS-induced acute lung injury.

Acute Disease↗
PubMed1993

[Two elderly cases with acute exacerbation of interstitial pneumonia].

We studied two cases of the elderly with acute exacerbation of interstitial pneumonia to elucidate a prognostic role of super oxide generation in peripheral whole blood. The first case was a 70-year-old man, who presented with acute exacerbation of interstitial pneumonia and was hospitalized. Following steroid-pulse therapy, CRP, ESR, blood-gas and his physical condition improved, resulting in successful discharge. In this case, super oxide generation standardized by the number of neutrophils (K) decreased to less than 1.0 in association with the improvement of physical condition. The second case was a 92-year-old woman in whom acute exacerbation of interstitial pneumonia was diagnosed. While the pulse therapy, CRP, LDH and blood-gas temporarily improved, K was continuously greater than 1.0 and the physical condition worsened, resulting in her death. These cases suggest that the measurement of super oxide generation in peripheral whole blood may play a useful role in assessing the prognosis of the elderly with acute exacerbation of interstitial pneumonia.

Acute Disease↗
PubMed1993

[Scanning electron microscopic study on inner ear barotrauma: in the guinea pig with one eustachian tube occluded].

In order to investigate the mechanism of inner ear barotrauma, guinea pigs, with one eustachian tube occluded, were subjected to compression and decompression between 1 absolute pressure and 2 absolute pressures in a high pressure chamber. The authors divided the animals into three groups according to the speed of compression and decompression. Each group contained 10 guinea pigs. Morphological changes in the cochlear sensory hairs were examined by means of scanning electron microscope. On the occluded side, hair cells were damaged more frequently and more severely by rapid compression than by rapid decompression. There was no difference in the degree of damage produced by slow decompression and rapid decompression. On the control side, slight or moderate damage to hair cells was observed mainly as a result of rapid decompression. These findings led us to hypothesize that, in the setting of normal eustachian tube function, inner ear barotrauma would generally be caused by the relative positive pressure in the middle ear cavity that occurs during decompression. Furthermore, animals deprived of eustachian tube function would not have sufficient endurance for rapid compression and would sustain inner ear barotrauma far more readily, and of far greater severity, with rapid compression than would animals with normal eustachian tube function. The difference may be due to the presence of another pressure transmission pathway to the inner ear. The mechanism of cochlear sensory hair damage due to atmospheric pressure changes is presumed to be distortion of the reticular lamina and cuticular plate caused by the difference in pressure between cortilymph (perilymph) and the subtectorial space (endolymph) resulting in injury to stereocilia.

Animals↗
PubMed1993

[Vestibular changes due to barotrauma].

Morphological vestibular changes caused by barotrauma were studied in guinea pigs. Animals were exposed to rapid decompression from 2 absolute atmospheric pressures (ATA) to 1 ATA, which causes inner ear barotrauma in the guinea pig. During decompression, spontaneous nystagmus was recorded, which consisted of irritative symptoms initially, followed by paralytic nystagmus. After pressure loading and observation to confirm the absence of Preyer's reflex with vertigo, the animals were tested for caloric nystagmus using ice water and then sacrificed at varying intervals. Then, morphological changes in vestibular organs and the organ of Corti were studied. Half of the experimental animals showed canal paresis on caloric testing. Damage to the organ of Corti was severe while that to vestibular organs was very slight. Damage to the sensory cells of the vestibular organs was not clear on light microscopy, despite a partial collapse of labyrinthine membranes. Under scanning electron microscopy, local damage was observed in a portion of the crista ampullaris of the semicircular canals. In this area, incomplete or complete disappearance of kinocilia and stereocilia, similar to that seen after rotatostimulation, was observed. However, no damage to sensory hairs was seen in the utricles and saccules. The observed vestibular organ damage, resulting from inner ear barotrauma, suggested effects on endolymphatic flow.

Animals↗
PubMed1993

Intestinal protection against Strongyloides ratti and mastocytosis induced by administration of interleukin-3 in mice.

Information about interleukin-3 (IL-3) effects in vivo is limited compared with the in vitro effects. We found that a repetitive injection of a low dose of recombinant IL-3 induced protection against intestinal worms of Strongyloides ratti in C57BL/6 mice. When mice were injected i.p. with different doses of recombinant IL-3 twice a day from day -5 to day -1 and infected orally with larvae recovered from the head of infected rats on day 0, worm recovery from the small intestine was markedly reduced by a total of 10(4) U IL-3 or more on day 2 post-infection. The number of intestinal mucosal mast cells (MMC) was increased by the protective dose of IL-3. The IL-3 treatment, however, was ineffective in protecting mice against tissue migrating larvae, as assessed by recovery from the head. The protective effect of IL-3 on intestinal worms was observed within 6 hr post oral infection, suggesting little concern with antigen-specific immune responses. The effective dose of IL-3 treatment increased the number of MMC progenitors five times in the spleen and the mesenteric lymph nodes. An MMC-specific protease, MMCP-1, was secreted 200 times more than in controls in the intestinal lumen by the IL-3 treatment. The IL-3 treatment induced no protection or mastocytosis in mast cell-deficient W/Wv mice. These results suggest that the IL-3-induced intestinal protection against S. ratti is mediated by MMC.

Animals↗
PubMed1993

The superoxide generation of neutrophils in normal and preeclamptic pregnancies.

OBJECTIVE: To determine whether preeclampsia enhances superoxide generation of neutrophils. METHODS: Samples were obtained from 12 normal nonpregnant, 15 normal pregnant, and 11 preeclamptic women. The superoxide production of neutrophils was measured by the superoxide dismutase-inhibitable reduction of ferricytochrome C at 550-540 nm using a dual-wavelength spectrophotometer. RESULTS: N-formyl-methionyl-leucyl-phenylalanine (FMLP)-induced superoxide production of neutrophils was significantly higher in preeclamptics than in normal nonpregnant and pregnant subjects, whereas phorbol 12-myristate 13-acetate-induced superoxide production did not differ among them. When neutrophils prepared from normal nonpregnant women were preincubated with sera from the study groups, sera from preeclamptics enhanced the FMLP-induced superoxide production to about twice that of the other subjects. The serum-enhancing factor appeared to be a heat-labile protein, different from other known activators. CONCLUSION: Preeclampsia is characterized by the presence of a neutrophil activator that enhances superoxide production. This enhanced production may contribute to the pathophysiologic changes observed in preeclampsia.

Adult↗
PubMed1993

Virus reactivation in bitches with a medical history of herpesvirus infection.

Virologic and pathologic investigations were done on prednisolone-treated bitches with a history of canine herpesvirus (CHV) infection. Reactivation of CHV was demonstrated in 5 Beagle bitches after daily administration of 600 mg of prednisolone for 5 days. The reactivation was confirmed in 4 of 5 bitches. Canine herpesvirus was recovered from nasal, oral, vaginal, and ocular secretions on the 5th to 21st days after initiation of treatment with prednisolone, and also from nasal mucosa and tonsil tissues. Results indicated that latent CHV infections develop and that the virus may be reactivated, without clinical signs, in dogs with a history of CHV infection.

Abortion, Veterinary↗
PubMed1993

Enhanced healing of large cranial defects by an osteoinductive protein in rabbits.

Two experimental bone-graft substitutes, one composed of a porous hydroxyapatite plus an osteoinductive protein and the other composed of lactomer beads (copolymers of polylactic acid and polyglycolic acid) plus an osteoinductive protein, were evaluated as a means of reconstructing a large cranial defect model created in the rabbit. Twenty-five rabbits underwent a 16 x 20 x 1.5 mm full-thickness (extradural) excision of the parietal bone, were divided into different groups of five rabbits each, and were reconstructed by (1) hydroxyapatite, (2) hydroxyapatite plus protein, (3) lactomer beads, and (4) lactomer beads plus protein, and (5) one group consisted of nonreconstructed controls. The implants were harvested at 12 weeks and analyzed for percentage of bone ingrowth by histologic examination of decalcified mid-coronal sections stained with hematoxylin and eosin. The groups reconstructed with protein-treated implants demonstrated significantly greater amounts of ingrowth than those with untreated implants. Both protein-treated hydroxyapatite and lactomer bead groups had more than twice the amount of bone ingrowth than their respective untreated groups (29.0 versus 12.8 percent, p < 0.005, and 27.0 versus 10.0 percent, p < 0.001, respectively). The new bone found in the protein-treated and untreated implants was quite different: lamellar and woven, respectively. The results strongly suggest a clinical role for the combination of the mechanisms of osteoconduction and osteoinduction in the treatment of bone defects.

Animals↗
PubMed1992

Inhibition by a novel azole antifungal agent with a geranyl group on lanosterol 14 alpha-demethylase of yeast.

AFK-108 (1-[2-(2,4-dichlorophenyl)-2-((2E)-3,7-dimethylocta-2,6- dienyloxy)ethyl]-1H-imidazole) is a new imidazole derivative characterized by a geranyl substituent showing strong antifungal activity. Azole antifungal agents are known to be potent inhibitors of lanosterol 14 alpha-demethylase (P450(14)DM) of fungi. The role of the geranyl group of AFK-108 on interaction of AFK-108 with the target was studied by using Saccharomyces cerevisiae P450(14)DM as the model enzyme. AFK-108 and some of its derivatives bound to oxidized P450(14)DM with one-to-one stoichiometry and inhibited the demethylase activity. AFK-108 derivatives having the longer farnesyl or the shorter prenyl group showed lower affinity than AFK-108 for the enzyme. AFK-108 caused 100% inhibition at the equivalent concentration to P450(14)DM in the reaction mixture (0.07 microM), while the farnesyl derivative inhibited the activity by 60% at the same concentration. AFK-108 interfered with the binding of CO to the ferrous P450(14)DM. However, the interfering effect of the prenyl derivative was lower than that of AFK-108. Another AFK-108 derivative having the saturated 3,7-dimethyloctyl group was also a weaker inhibitor than AFK-108. These experiments suggest that the geranyl group of AFK-108 interacts with the substrate binding site of P450(14)DM that recognises the side chain of the substrate. AFK-108 is the first example of an azole derivative interacting with the side chain recognising region of the substrate binding site of P450(14)DM.

Antifungal Agents↗